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Role of cannabinoids and vitamin E analogues in macrophages foam cells formation

Grant number: 19/21551-1
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): September 01, 2020
Effective date (End): January 31, 2021
Field of knowledge:Health Sciences - Nutrition
Principal Investigator:Vivian Marques Miguel Suen
Grantee:Caroline Bertoncini Silva
Supervisor abroad: Jean-Marc Zingg
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Local de pesquisa : University of Miami, United States  
Associated to the scholarship:18/06094-0 - Lipid, inflammatory and intestinal microbiota profile of mice fed a high-fat diet submitted to supplementation with different doses of curcumin, BP.DR


Cannabinoid receptors and their ligands have emerged as important regulators of cardiometabolic diseases such as dyslipidemia, obesity and atherosclerosis. Activation of cannabinoid receptors by selective agonists can increase macrophages lipids accumulation and foam cells formation, events that could be inhibited by the antagonist cannabidiol. Lipids accumulation in monocytes and macrophages was triggered by modulating the expression of CD36/FAT scavenger receptor/fatty acids transporter and ABCA1/G1 cholesterol transporter as well as of inflammatory cytokines, events that could be inhibited by selective cannabinoid receptor antagonists. Several vitamin E analogues have been previously shown to reduce lipids accumulation in monocytes and macrophages in response to oxidized low density lipoproteins (oxLDL), but the molecular mechanisms are not completely resolved and may involve CD36-mediated regulatory effects on signal transduction and gene expression. Recently, an increased number of foam cells was detected in bronchoalveolar lavages and lungs in cases of vaping-associated pulmonary injury (VAPI) after inhaling e-cigarette smoke from products containing cannabinoids and possibly the vitamin E analogue, alpha-tocopherol acetate (alpha-TA). To date, the role of vitamin E analogues in cannabinoid-induced foam cell formation has not been investigated. Therefore, in this project we will analyze whether vitamin E analogues and in particular alpha-TA affects foam cells formation in human monocytes and macrophages in response to oxLDL and cannabinoids. (AU)